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Biomedical subjects

J M O'Brien

Publications and source records attributed to J M O'Brien.

At least 91 records · Page 5Linked to original sources
PubMed1991

Adolescents' reactions to the death of a peer.

In recent years, more attention has been given to the fact that grieving is a process, especially in the work of Elizabeth Kubler-Ross. The literature has focused on many aspects of bereavement, including how the process may be different at different ages. Much of the research on adolescents has focused on reactions to the suicide of a peer. The purpose of this study was to explore adolescent reactions to the death of a peer by means other than suicide. Semistructured interviews were conducted with ten college students about their experience of losing a friend in high school. Results indicated that even after a few years, the adolescents were still struggling through the grieving process. Implications for future research and suggestions for practitioners faced with similar crises are offered.

Adolescent↗
PubMed1991

Primitive neuroectodermal tumor of the midbrain in a murine model of retinoblastoma.

The first heritable model of retinoblastoma was established by retina-specific expression of simian virus 40 T-antigen (SV40 T-ag) in transgenic mice. Bilateral, multifocal ocular tumors were observed in 100% of transgene-bearing mice. Central nervous system neoplasms occurred at a lower rate (27%) and represented the murine counterpart of human trilateral retinoblastoma. The authors characterized the transgenic brain tumors and found them to be primitive neuroectodermal tumors (PNET) of the midbrain. Murine brain tumors do not involve the pineal gland and most closely resemble undifferentiated suprasellar or parasellar tumors occasionally observed in human trilateral retinoblastoma. The murine malignancies arose from the subependymal cells of the cerebral aqueduct. Immunohistochemical and ultrastructural examination revealed that the transgenic brain tumors were undifferentiated and lacked all antigens associated with normal murine neuronal, glial, and ependymal cells.

Animals↗
PubMed1990

Isolation and sequence analysis of CDC43, a gene involved in the control of cell polarity in Saccharomyces cerevisiae.

The Saccharomyces cerevisiae CDC43 gene product is involved in establishing cell polarity during the cell-division cycle. When grown at restrictive temperatures, temperature-sensitive cdc43 mutants are unable to form buds and display delocalized cell-surface deposition [Adams et al., J. Cell Biol. (1990) in press]. We have isolated a cdc43-complementing plasmid from a yeast genomic-DNA library and localized the CDC43 gene, by subcloning and transposon-mutagenesis experiments, to a 1.2-kb region of DNA that contained only one significant ATG-initiated open reading frame of 213 codons. The putative CDC43 gene product contains a possible nuclear-localization signal sequence, a cysteine-rich domain and a histidine-rich domain, and a region that is similar in structure to alpha-helix-turn-alpha-helix structural domains present in some prokaryotic and eukaryotic DNA-binding proteins.

Alkyl and Aryl Transferases↗
PubMed1990

Retinoblastoma in transgenic mice.

Retinoblastoma, a malignancy of the eye occurring in young children, has been widely studied as a model for genetic predisposition to cancer. This disease is caused by mutations in both alleles of an anti-oncogene (the retinoblastoma gene, Rb) that inactivate or eliminate the Rb encoded protein, p105Rb (refs 1 and 2). Here we report that expression of a viral oncogene, the simian virus 40 T antigen, in the retina of transgenic mice produces heritable ocular tumours with histological, ultrastructural and immunohistochemical features identical to those of human retinoblastoma. Furthermore, we demonstrate a specific association between p105Rb and T antigen in mouse retinoblastoma tumour cells. Thus, the occurrence of these tumours is in vivo evidence for oncogenesis due to the ocular-specific expression of an Rb-binding oncoprotein that can functionally inactivate the Rb protein. As an animal model for heritable retinoblastoma, these mice should allow the study of the ontogeny, pathogenesis and treatment of this malignant disease.

Animals↗
PubMed1990

A transgenic mouse model for trilateral retinoblastoma.

We present a murine model of trilateral retinoblastoma. Ocular retinoblastoma and central nervous system tumors are observed in a line of mice formed by the transgenic expression of SV40 T-antigen. An oncogenic protein known to bind to the retinoblastoma gene product (p105-Rb) is specifically expressed within retinal cells in this model. All animals that carry this genetic alteration develop multifocal retinal tumors. Midbrain tumors are observed in 15% of ocular tumor-bearing animals, and these arise ventral to the cerebral aqueduct at the level of the pineal gland. Both ocular and central nervous system neoplasms are heritable in heterozygous offspring through 10 sequential generations of breeding. Retinal tumors display the gross appearance, invasive properties, light and electron microscopic features, and immunohistochemical staining characteristics of human retinoblastoma. The light and electron microscopic characteristics as well as immunocytochemical features of undifferentiated midline central nervous system neoplasms further correlate with human trilateral retinoblastoma. We postulate an alternative mechanism of retinoblastoma tumorigenesis that involves functional inactivation of retinoblastoma protein locally in the face of an intact retinoblastoma gene locus.

Animals↗
PubMed1990

Evaluation of merocyanine 540-sensitized photoirradiation as a means to inactivate enveloped viruses in blood products.

Dry or wet heat, solvents, and detergents combined with ultraviolet irradiation provide effective means of sterilizing soluble blood products such as albumin or factor VIII. For obvious reasons, these procedures are not applicable to cellular blood components. We have recently shown that simultaneous exposure to the photosensitizer, merocyanine 540 (MC 540) and white light rapidly inactivates the Friend erythroleukemia virus complex and Friend virus-transformed cells, but causes relatively little damage to pluripotent hematopoietic stem cells. In this communication, we show that several lipid-enveloped human pathogenic viruses are also highly susceptible to MC 540-sensitized photoirradiation, and we report on an initial evaluation of the ability of MC 540-sensitized photoirradiation to sterilize blood products.

2,3-Diphosphoglycerate↗
PubMed1989

Therapeutic approaches for ophthalmic problems in juvenile rheumatoid arthritis.

Juvenile rheumatoid arthritis is a disease of children which is chronic and painful, with the potential to produce permanent disability and blindness in a significant portion of cases. The treatment we provide these children may also disable them. Managing this disease process and caring for these patients is a challenging task in which therapeutic efficacy must be continually balanced against treatment morbidity. With respect to ocular disease, we must particularly recognize the difficulties parents have in treating a characteristically asymptomatic process with interventions that can produce unpleasant symptomatology. The importance of discussion of therapeutic decisions with parent and child cannot be overemphasized. Children with JRA should be carefully classified and those at greatest risk for development of ocular disease should receive frequent ophthalmologic screening exams. Early intervention and aggressive medical management of intraocular inflammation will minimize morbidity and permanent visual compromise. Patients should also be closely monitored for ocular side effects of therapies directed against articular disease. Procedures employed for treatment of cataract, glaucoma, corneal, and vitreal opacities must take into account the risk and complications of surgical intervention in the JRA patient prone to perioperative inflammation.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1989

Male factor infertility.

Male factors are responsible for or contributory to half of infertility cases. Through history, physical exam, and basic tests, the clinician can successfully perform the majority of evaluations. The use of semen analysis, postcoital test, and serum hormonal levels are described. Causal factors are discussed. The use of more specialized testing and information concerning referral are also detailed.

Humans↗
PubMed1989

Inactivation of Friend erythroleukemia virus and Friend virus-transformed cells by merocyanine 540-mediated photosensitization.

The Friend virus complex was used as a model to study the effects of merocyanine 540 (MC 540)-mediated photosensitization on enveloped viruses. Simultaneous exposure to the lipophilic dye MC 540 and white light inactivated cell-free virus, cell-associated virus, and virus-transformed cells. When used under experimental conditions that are known to preserve most mature blood cells, at least some coagulation factors, and a significant portion of the pluripotent hematopoietic stem cell compartment, MC 540-mediated photosensitization reduced virus titers by greater than or equal to 4 log and the concentration of in vitro clonogenic erythroleukemia cells by greater than or equal to 5 log. Animals that received a single intravenous injection of photosensitized virus were resistant to a subsequent challenge with live virus. High sensitivity to MC 540-mediated photosensitization appears to be a property that is shared by other enveloped viruses. Thus, photosensitization mediated by MC 540 may be of benefit in the sterilization of blood products (in particular, cellular products), the production of vaccines, and selected areas of antiviral therapy.

Animals↗
PubMed1989

Mutagenicity of merocyanine 540-mediated photosensitization.

Merocyanine 540 (MC 540) is a photosensitizing dye with antineoplastic and antiviral properties. Because photoexcited MC 540 generates singlet molecular oxygen and possibly other reactive oxygen species there is concern that MC 540-mediated photosensitization may be mutagenic. In this paper, we report on the induction of ouabain- and 6-thioguanine-resistant mutants in Chinese hamster ovary (CHO) cells by MC 540 and light. Incubation with merocyanine 540 in the dark was not mutagenic. Simultaneous exposure to dye and high-intensity (70-75 W/m2) white or green light caused a small but significant increase in the frequency of both ouabain- and 6-thioguanine-resistant mutants. Similar increases in mutation frequencies were observed when the cells were exposed to white or green light in the absence of dye. When the fluence rate of the white light source was reduced by 50% (i.e., to 35 W/m2) but the duration of exposure doubled to keep the fluence constant, dye-mediated photosensitization and exposure to light alone generated few if any mutants. These results indicated that MC 540-mediated photosensitization is not mutagenic (as defined by the employed assays) as long as a nonmutagenic light source is used to excite the photosensitizer. They caution against the use of very powerful light sources in clinical applications of MC 540-mediated photosensitization.

Animals↗
PubMed1988

[3H]dexamethasone binding to plasma membrane-enriched fractions from liver of nonadrenalectomized rats.

Using liver from nonadrenalectomized adult male rats, binding sites for [3H]dexamethasone in particulate fractions are demonstrated. The binding is thermolabile, saturable, and specific for glucocorticoid. The apparent dissociation constant (Kdapp) for [3H]dexamethasone (0.48 +/- 0.084 microM) is 60-fold greater than that for cytosolic receptor (7.9 +/- 1.5 nM). The Kdapp for [3H]cortisol in particulate fractions is 2.5-fold lower than for [3H]dexamethasone (Kdapp = 0.18 microM). The binding capacities for particulate and cytosolic glucocorticoid-binding sites also differ significantly, with particulate sites at least 9.1-fold more concentrated than cytosolic sites in liver tissue. Particulate sites are determined in Percoll density gradients to have a density of 1.039 g/cc. Saturable [3H]dexamethasone radioactivity coelutes from these gradients with the plasma membrane marker enzyme 5'-nucleotidase. Adrenalectomy causes the complete loss of particulate binding sites by 6 days postadrenalectomy; however, these sites can be regenerated to two thirds of the nonadrenalectomy level by 20-30 days postadrenalectomy.

Adrenal Glands↗
PubMed1988

Obstetric ultrasound training for family physicians. Results from a multi-site study.

A practical program to train family physicians in obstetric ultrasound was tested with 13 family physicians. Each physician completed 6.5 days of course work and ultrasound laboratory apprenticeship prior to beginning a clinical preceptorship of approximately 14 months' duration. During the clinical preceptorship the physicians performed ultrasound studies in their own offices. All studies were reviewed by a local consultant radiologist utilizing examination data sheets and videotapes. At the conclusion of the training program, the physicians took a combined practical and written proficiency examination administered by an independent sonographer. Eight physicians completed the training, performing during the preceptorship an average of 78 examinations. The rated performance of the physicians improved markedly over the course of the preceptorship. During the last segment of the preceptorship the radiologist preceptors rated 94 percent of the ultrasound studies as acceptable, compared with 79 percent rated acceptable at the beginning of the preceptorship. Seven of the eight physicians completing the protocol took the proficiency examination: all passed. This study can provide a blueprint for an individual family physician to design his own training, or it can guide an academic department of family medicine in developing and evaluating ultrasound training programs for residents and practicing physicians.

Education, Medical, Continuing↗
PubMed1988

Xanthogranulomatous pyelonephritis. A reappraisal and immunohistochemical study.

The clinicopathologic features of 17 patients with xanthogranulomatous pyelonephritis are described, together with results on a number of histochemical and immunohistochemical techniques that were used to demonstrate the variety of cells involved. Based on our clinicopathologic data and review of the literature, we believe that xanthogranulomatous pyelonephritis should be regarded as a destructive, and, at times, tumefactive inflammatory process that may complicate chronic pyelonephritis. The initiation of this process remains an enigma. However, there appears to be three main features that are associated with xanthogranulomatous pyelonephritis: pelvicalyceal obstruction, ulceration of the pelvicalyceal urothelium, and bacterial infection.

Adult↗